Randomised controlled trial of isoniazid preventive therapy in South African adults with advanced HIV disease.

BACKGROUND: Tuberculosis (TB) preventive therapy is not effective in human immunodeficiency virus (HIV) infected adults with negative tuberculin skin tests (TSTs). However, there are insufficient data on patients with advanced HIV disease from high TB incidence areas. METHODS: We conducted a randomised, double-blind, controlled trial comparing isoniazid (INH) with placebo among TST-negative adults with World Health Organization Stage 3 or 4 HIV disease. INH/placebo was administered for 12 months by patient-nominated supervisors. TST-positive participants were given open-label INH. Participants, who did not have access to antiretroviral therapy (ART), were followed up for 24 months with 6-monthly sputum culture and chest radiography. RESULTS: A total of 118 participants were enrolled: TST was negative in 98. In the randomised arms, the incidence of TB was 18/100 person-years (py) in the INH arm and 11.6/100 py in the placebo arm (hazard ratio 1.59, 95%CI 0.57-4.49). There were no significant differences in mortality, hospitalisation rate or CD4+ lymphocyte decline. INH/placebo adherence was 85%, and was significantly higher among participants with work-based treatment supervisors. CONCLUSIONS: We did not find any association between INH preventive therapy and reductions in incident TB among TST-negative adults with advanced HIV disease, but the study had limited statistical power. High levels of adherence were observed with patient-nominated supervisors.     

Tolerability of anti-tuberculosis treatment and HIV serostatus.

SETTING: Tuberculosis (TB) is frequent in human immunodeficiency virus (HIV) infected patients, but its treatment is hampered by adverse events and paradoxical reactions. OBJECTIVE: To examine the impact of HIV infection and other factors on the risk and spectrum of adverse events related to anti-tuberculosis treatment in a prospective cohort study conducted between January 2003 and August 2004. RESULTS: Of 105 patients treated for TB, 30 were HIV-infected. The overall incidence of adverse events was 122.5 +/- 18.5 per 100 patient-years (py) and the incidence of severe adverse events was 45.2 +/- 11.3/100 py. Age >50 years (OR 2.2, 95%CI 1.01-4.8, P = 0.046) and HIV infection (OR 3.9, 95%CI 2.1-7.5, P < 0.001) were independently associated with a higher risk of adverse events. Hepatitis (30.5/100 py) and neuropathy (28.6/100 py) were the most frequent adverse events. Hepatitis C virus infection was associated with hepatitis (OR 4.2, 95%CI 1.2-15.0, P = 0.028) and neuropathy with HIV infection (OR 3.8, 95%CI 1.1-13.7, P = 0.040). CONCLUSION: Adverse reactions to anti-tuberculosis drugs are frequent. HIV infection and age >50 years are factors associated with such reactions, while hepatitis C virus infection is a risk factor for hepatitis.     

Contribution of reinfection to recurrent tuberculosis in South African gold miners

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.     

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.     

INH preventive therapy among adult HIV-infected patients in Thailand.

SETTING: Two HIV/AIDS clinics in Bangkok. OBJECTIVE: Although isoniazid (INH) preventive therapy (IPT) can reduce the risk of active TB among HIV-infected individuals, preventive therapy is rarely used in developing countries. The WHO recommends INH prophylaxis for tuberculin skin test (TST) positive HIV positives or for all HIV positives in countries with a high prevalence of latent TB if TST is unfeasible. It is not known whether IPT without TST will affect adherence. DESIGN: Prior to receiving IPT, 914 HIV-infected patients in Bangkok were randomized to TST or not. Adherence, measured by self-report and pill counts, and proportion completing therapy were evaluated. RESULTS: Adherence was 84.5% and 79.7%, by self-report, and 81.8% and 73.9% by pill count, respectively, in PPD-positive and non-TST-screened subjects (adjusted OR 1.44, 95%CI 0.79-2.64 and 1.53, 95%CI 0.45-5.26). The drop-out rate before treatment was 6.3% in the TST-screened and 1.7% in the non-TST screened subjects (OR 3.93, 95%CI 1.18-16.04). CONCLUSION: TST screening was not a predictor of adherence to IPT once therapy began, but it was associated with a higher drop-out rate prior to therapy. Acceptable levels of adherence were observed with both regimens.     

Risk of development of tuberculosis in HIV-infected patients.

OBJECTIVE: To estimate the rate of development of active tuberculosis (TB) in a cohort of human immunodeficiency virus (HIV) positive patients, and to identify the characteristics of these patients. DESIGN: A total of 175 HIV-positive individuals were recruited from clinics for sexually transmitted diseases and followed up for 31 +/- 6.8 months. Clinical examination, chest X-ray, sputum smear for acid-fast bacilli and culture for mycobacteria and HIV serology were performed at the time of registration and repeated periodically. RESULTS: Seventeen patients had TB at intake and another 24 developed TB during follow-up, giving a breakdown rate of 6.9/100 person-years (p-y) (95% confidence interval [CI] 4.1-9.6). The attack rates were similar in tuberculin positive (7.1/100 p-y, 95%CI 3.4-10.8) and negative (6.7/100 p-y, 95%CI 2.6-10.8) patients. There was a trend towards higher mortality in patients who developed TB (10.5/100 p-y, 95%CI 4.8-15.2) compared to those who did not (6.1/100 p-y, 95%CI 3.2-8.8). CONCLUSIONS: The results of this study provide information regarding the high risk of development of active tuberculosis and its associated mortality in HIV-infected persons. The risk of developing TB appears to be equally high in tuberculin positive and negative individuals, suggesting that new infections could play a major role in this susceptible population.     

Rifampicin plus pyrazinamide versus isoniazid for treating latent tuberculosis infection: a meta-analysis.

SETTING: Six trials from Haiti, Mexico, the U.S.A., Brazil, Spain, Zambia and Hong Kong. OBJECTIVE: To evaluate the efficacy and safety of rifampicin plus pyrazinamide (RZ) vs. isoniazid (INH) for the prevention of tuberculosis (TB) among persons with or without human immunodeficiency virus (HIV) infection. DESIGN: Meta-analysis of randomised controlled trials (RCTs) and quasi-RCTs that compared RZ for 2-3 months with INH for 6-12 months. Endpoints were development of active TB, severe adverse effects and death. Treatment effects were summarised as risk difference (RD) with 95% confidence intervals (CI). RESULTS: Three trials conducted in HIV-infected patients and three trials conducted in non-HIV-infected persons were identified. The rates of TB in the RZ group were similar to those in the INH group, whether the subjects were HIV-infected or not (HIV-infected patients: pooled RD = 0%, 95% CI -1-2, P = 0.89; non-HIV-infected persons: pooled RD = 0%, 95% CI -2-1, P = 0.55). There was no difference in mortality between the two treatment groups (HIV-infected patients: pooled RD = -1%, 95% CI -4-2, P = 0.53; non-HIV-infected persons: pooled RD = 0%, 95% CI -1-1, P = 1.00). However, both subgroup analyses showed that a higher incidence of all severe adverse events was associated with 2RZ than INH among non-HIV-infected persons (RD = 29%, 95% CI 13-46, P = 0.0005 vs. RD = 7%, 95% CI 4-10, P < 0.0001). CONCLUSION: RZ is equivalent to INH in terms of efficacy and mortality in the treatment of latent tuberculosis infection. However, this regimen increases the risk of severe adverse effects compared with INH in non-HIV-infected persons.     

Low CD4+ T-cell count and high HIV viral load precede the development of tuberculosis disease in a cohort of HIV-positive ethiopians.

SETTING: Prospective cohort study, Ethiopia. OBJECTIVE: To study changes in biological markers of HIV infection progression before and after development of TB disease. DESIGN: A longitudinal study of 804 adult factory workers (95 HIV-positive, 709 HIV-negative), who were followed every 6 months for a median of 3.8 years. RESULTS: Overall, the incidence rate of TB was 10/ 222 = 45.1 (95%CI 24.3-83.9) per 1000 person-years of observation (PYO) among HIV-1-positive participants, compared to 14/2,054 = 6.8 (95%CI 4.0-11.5) per 1,000 PYO among HIV-1-negative participants (incidence rate ratio 6.62, 95%CI 2.94-14.9). Among the 10 HIV-positive participants who subsequently developed TB disease, the CD4 count was low (median 201/microl, range 45-419), and viral load high (median 4.97 log copies/ml, range 3.70-5.58), at the routine follow-up visit prior to TB diagnosis. Following TB treatment, plasma viral load remained persistently elevated despite clinical resolution of TB disease, and seven of the 10 patients died within a median time of 8 months. CONCLUSION: In this cohort, HIV-infected Ethiopians who developed TB disease already had low CD4 counts and high viral load prior to the diagnosis of TB. Viral load did not decrease following TB treatment, leading to a poor overall prognosis in these patients.     

Incidence of tuberculosis and the importance of treatment of latent tuberculosis infection in a Spanish prison population.

OBJECTIVE: To establish the incidence of tuberculosis (TB) in a prison population and its link with latent tuberculosis infection treatment (LTIT). METHODS: From 1991 to 1999 a TB programme was run in a Spanish prison. A cohort study was conducted to know TB incidence and the associated variables. RESULTS: Of 1,050 people studied, 10% were co-infected by the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. Twenty-three cases of TB were detected, an incidence rate of 6.39 per 1,000 person-years of follow-up. Multivariate analysis showed HIV-infected patients (RR 4.07, 95%CI 2.61-6.35), and those infected by M. tuberculosis who did not undergo LTIT (RR 10.15, 95%CI 0.90-50.59) to be at greater risk of developing TB. In TST reactors, those co-infected with HIV (RR 10.15, 95%CI 3.80-27.07) and those who had not undergone LTIT (RR 8.53, 95%CI 1.12-64.86) were shown to be at the greatest risk of developing TB. CONCLUSIONS: The observed incidence of TB is much higher in prisons than in the community at large. HIV-M. tuberculosis co-infection appears as the main risk factor for developing TB, while LTIT significantly reduces incidence.     

Recurrent tuberculosis and its risk factors: adequately treated patients are still at high risk.

Recurrent tuberculosis (TB) poses significant threats, including drug resistance, to TB control programs. However, recurrence and its causes, particularly in the era of epidemic human immunodeficiency virus (HIV), have not been well described. We systematically searched published material for studies reporting on recurrent TB following completion of standard treatment regimens to provide data on the issue. A total of 32 studies were reviewed. Among controlled trials, the overall recurrence rates (per 100,000 person-years) were respectively 3,010 (95%CI 2,230-3,970) and 2,290 (95%CI 1,730-2,940) at 6 and 12 months after treatment completion. Recurrence rates were higher among observational studies compared to controlled trials and in countries with high versus low background TB incidence. TB recurrence (%) was higher among HIV-infected (6.7, 95%CI 5.9-7.6) than non-HIV-infected individuals (3.3, 95%CI 2.8-3.9). Factors independently associated with recurrence in the literature included residual cavitation, greater area of involved lung tissue, positive sputum culture at 2 months of treatment and HIV infection. Among those with HIV infection, recurrent TB was associated with a low initial CD(4) count and receiving less than 37 weeks of anti-tuberculosis treatment. We argue that adequately treated patients are still at high risk for recurrent disease and should be considered in case-finding strategies. Moreover, those with multiple risk factors may benefit from modification of standard treatment.     

Risk of Mycobacterium tuberculosis infection and disease among health care workers, Chiang Rai, Thailand.

SETTING: A provincial referral hospital in northern Thailand, where a cross-sectional study during 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission. OBJECTIVE: To describe the effectiveness of prevention strategies for nosocomial tuberculosis (TB). DESIGN: A prospective study among health care workers (HCW) including annual tuberculin skin test (TST) screening and active TB surveillance. Following a comprehensive risk assessment, preventive interventions were implemented targeting HCWs, hospitalised patients, and the hospital environment. RESULTS: The number of pulmonary TB cases diagnosed increased steadily from 102 in 1990 to 356 in 1999. The TST conversion rate was 9.3 (95% CI 3.3-15) per 100 person-years (py) in 1995-1997, but declined steadily to 2.2 (95% CI 0.0-5.1) in 1999. HCWs first screened within 12 months of employment had higher TST conversion rates (adjusted RR = 9.5, 95% CI 1.8-49.5) compared to those employed for longer than 12 months. The annual rate of active TB per 100 000 HCWs was 536 in 1995-1999. CONCLUSION: These HCWs were exposed to active TB patients and were at risk for M. tuberculosis infection, particularly during their first 12 months of employment. Implementation of nosocomial TB control measures in 1996 was followed by declining TST conversion rates, despite increasing exposure to active TB patients.     

Drug-resistant tuberculosis and HIV in Ukraine: a threatening convergence of two epidemics?

OBJECTIVE: To investigate anti-tuberculosis (TB) drug resistance rates in Donetsk Oblast, Ukraine, and to explore the association between the epidemics of human immunodeficiency virus (HIV) and multidrug-resistant TB (MDR-TB). METHODS: All consecutive newly diagnosed and previously treated patients with sputum smear-positive TB presenting to all TB units in Donetsk Oblast over 12 months were invited to take part in the study. A total of 1293 and 203 patients with TB were tested for HIV and MDR-TB in the civilian and penitentiary sectors, respectively. RESULTS: Of those enrolled for the study, 307 were HIV-positive, 379 had MDR-TB, and 97 had MDR-TB and HIV co-infection. MDR-TB rates in the civilian sector were respectively 15.5% (95%CI 13.1-17.8) and 41.5% (95%CI 36.4-46.5) in newly diagnosed and previously treated TB patients. Among prisoners, MDR-TB rates were 21.8% (95%CI 12.4-31.2) in new cases and 52.8% (95%CI 43.9-61.7) in previously treated TB cases. HIV status was significantly associated with MDR-TB (OR 1.7, 95%CI 1.3-2.3). CONCLUSIONS: High MDR-TB rates and a positive association between MDR-TB and HIV epidemics were found in Donetsk Oblast. Urgent measures to improve HIV prevention, control of drug-resistant TB and collaboration between HIV and TB control activities need to be implemented without further delay.     

Does antiretroviral treatment reduce case fatality among HIV-positive patients with tuberculosis in Malawi?

SETTING: Thyolo district, Malawi. OBJECTIVES: To report on 1) case fatality among human immunodeficiency virus (HIV) positive tuberculosis (TB) patients while on anti-tuberculosis treatment and 2) whether antiretroviral treatment (ART) initiated during the continuation phase of TB treatment reduces case fatality. DESIGN: Retrospective cohort analysis. METHODS: Comparative analysis of treatment outcomes for TB patients registered between January and December 2004. RESULTS: Of 983 newly registered TB patients receiving diagnostic HIV testing, 658 (67%) were HIV-positive. A total of 132 (20%) patients died during the 8-month course of anti-tuberculosis treatment, of whom 82 (62%) died within the first 2 months of treatment when ART was not provided (cumulative incidence 3.0, 95%CI 2.5-3.6 per 100 person-years). A total of 576 TB patients started the continuation phase of anti-tuberculosis treatment, 180 (31%) of whom were started on ART. The case-fatality rate per 100 person-years was not significantly different for patients on ART (1.0, 95%CI 0.6-1.7) and those without ART (1.2, 95%CI 0.9-1.7, adjusted hazard ratio 0.86, 95%CI 0.4-1.6, P = 0.6) CONCLUSIONS: ART provided in the continuation phase of TB treatment does not have a significant impact on reducing case fatality. Reasons for this and possible measures to reduce high case fatality in the initial phase of TB treatment are discussed.     

Adverse drug reactions associated with first-line anti-tuberculosis drug regimens.

BACKGROUND: Standard treatment of active tuberculosis (TB) consists of isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment. OBJECTIVES: To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications. METHODS: This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated. RESULTS: A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >or=60 years, baseline aspartate aminotransferase >or=80 U/l and drug resistance were associated with any major event. CONCLUSIONS: First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.     

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.     

Tuberculosis among health care workers at King Chulalongkorn Memorial Hospital, 1988-2002.

SETTING: It is still not well determined whether health care workers (HCWs) in developing countries-where background tuberculosis (TB) prevalence in the general population is high-have a higher risk of TB than other occupations. OBJECTIVE: To examine the risk of TB among HCWs in an area where TB prevalence is high. DESIGN: A cohort of 3959 HCWs at Chulalongkorn Memorial Hospital, Thailand, was observed from 1988 to 2002. RESULTS: The overall TB incidence rate was 188 per 100 000 person-years (py), with specific incidence rates of 77, 48 and 63/100 000 py, respectively, for confirmed, possible and self-reported TB cases. The highest risk work site was the emergency room, with rate ratios (RRs) of 10.4 (95%CI 3.0-44.7), 22.6 (95%CI 2.7-1041.2) and 9.4 (95%CI 1.5-99.1) for overall, confirmed and possible TB cases, respectively. The 11 TB cases in this area were 9 registered nurses, 1 nursing auxiliary and 1 housekeeper. The occupation of highest risk was nurse, with RRs of 2.4 (95%CI 0.9-9.1) for overall TB cases. However, only the increased RRs for the emergency room were statistically significant. CONCLUSION: The results of this study support the premise that certain groups of HCWs in developing countries are occupationally at increased risk of TB.     

The epidemiology of HIV-associated tuberculosis in rural Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: The World Health Organization recommends human immunodeficiency virus (HIV) testing for all tuberculosis (TB) patients and TB screening for all HIV-infected persons in countries with a TB-HIV syndemic. We sought to determine whether evidence supports implementing these recommendations in South-East Asia. DESIGN: We conducted a cross-sectional survey and retrospective cohort study of patients newly diagnosed with HIV or TB from October 2003 to February 2005 to identify risk factors for HIV infection and TB, and for death during TB treatment. RESULTS: HIV infection was diagnosed in 216/574 (38%) TB patients. TB disease was found in 124/450 (24%) HIV-infected persons. No sub-groups of patients had a low risk of HIV infection or TB. Of 180 TB patients with HIV infection and a recorded treatment outcome, 49 (27%) died compared to 17/357 (5%) without HIV infection (relative risk [RR] 5.2, 95% confidence interval [CI] 3.1-8.7). HIV-infected TB patients with smear-negative pulmonary disease died less frequently than those with smear-positive pulmonary disease (RR 0.39, 95%CI 0.16-0.93). CONCLUSIONS: No sub-groups of patients had low risk for HIV infection or TB, and mortality among HIV-infected TB patients was high. These data justify using the WHO global TB-HIV recommendations in South-East Asia. Urgent interventions are needed to reduce the high mortality rate in HIV-infected TB patients.     

Impact of tuberculosis on the course of HIV-infected patients with a high initial CD4 lymphocyte count.

OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of human immunodeficiency virus (HIV) infection in patients without immunological impairment. MATERIAL AND METHODS: In an observational study of retrospective cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB. Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l) and date of starting follow-up (+/-6 months). The progression of HIV infection was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200 x 10(6)/l; 2) clinical progression: time to development of acquired immune-deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease progression: time to the first defined event in 1, 2 and/or 3. The times to these events were estimated using Kaplan Meier curves. RESULTS: There were no significant differences between the cohorts for age, sex and risk group. Faster immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53-9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09; P < 0.01) were found in the cohort of TB patients. These associations were still significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x 10(6)/l) was related to greater progression to AIDS and shorter survival.     

Tuberculosis risk among staff of a large public hospital in Kenya

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.     

Evaluation of the Arkansas method of urine testing for isoniazid in South Africa.

SETTING: A South African hospital serving gold mine employees. OBJECTIVE: To determine the sensitivity and specificity of the Arkansas method for detecting isoniazid (INH) metabolites among South African adults and to examine the effect of smoking status on positive results. DESIGN: Urine specimens were collected from in-patients taking INH as part of tuberculosis treatment at 6, 12 and 24 h after a directly observed 300 mg oral dose. As a control group, a single urine specimen was collected from surgical in-patients not taking INH. Specimens were tested for INH using a commercially available dipstick. RESULTS: A total of 153 patients on INH and 60 controls were recruited. The sensitivity of the test was 93.3% (95%CI 88.1-96.8) at 6 h post INH, 93.4% (95%CI 88.2-96.8) at 12 h and 77% (95%CI 69.1-83.7) at 24 h. The specificity of the test was 98.3% (95%CI 91.1->99.9). There was no association between smoking status and colour change of positive results. CONCLUSIONS: This test is a useful method of monitoring adherence to TB treatment or preventive therapy among South Africans. However, it is less than 100% sensitive, especially with increasing time post dose, which should be taken into consideration when interpreting results for individual patients.